Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Abstract

Background: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis.Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. Methods: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based cosegregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. Results: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotypephenotype correlations were revealed as well. Conclusion: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan. K E Y W O R D Sinherited retinal dystrophy, mutations spectrum, Taiwanese population, targeted exome sequencing

Genotypes Predispose Phenotypes—Clinical Features and Genetic Spectrum of ABCA4-Associated Retinal Dystrophies

“…Few studies have been conducted on ABCA4-associated retinal dystrophies in Taiwan. Chen et al reported that CYP4V2 and USH2A were the most common disease-causing genes in Taiwanese IRD patients, and ABCA4 in China [23,24]. However, most of the patients recruited in that study had a phenotype of RP, which may lead to selection bias in genetic epidemiology.…”

Diverse Genetic Landscape of Suspected Retinitis Pigmentosa in a Large Korean Cohort

“…From previous studies, EYS variants account for the largest portion of causative genes in the East Asian region, especially in Korea and Japan; EYS variants account for 20 to 30% of RP cases, and USH2A variants cause less than 10% [ 16 , 17 , 18 ]. On the other hand, USH2A variants make up 20 to 40% and EYS variants account for less than 10% of RP cases, among the total RP population in Western or European ethnicities [ 8 , 19 , 20 ] as well as Chinese or Taiwanese populations [ 7 , 21 ]. The ratios of EYS and USH2A in our study were slightly lower than those in previous studies, which shows the unique genetic characteristics of Korean patients even in comparison with those of the other East Asian nations [ 18 ].…”

Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

“…In addition, we have not investigated the impact of copy number variation (Huang et al, 2017) and somatic mosaicism (Jin et al, 2007) in these patients. Finally, targeted exome sequencing including a panel of disease-causing genes, likewise the strategy of inherited retinal dystrophy (Huang et al, 2013(Huang et al, , 2015Xing et al, 2014;Chen et al, 2020), might be more appropriate for future genetic diagnosis of genetic HM.…”